P1039: LOW DOSE CYTARABINE FOR ADULT PATIENTS WITH NEWLY DIAGNOSED LANGERHANS CELL HISTIOCYTOSIS: A SINGLE ARM, SINGLE CENTER, PROSPECTIVE PHASE 2 STUDY
Authors: Long Chang, Min Lang, Minghui Duan, Jian LI, Dao-Bin Zhou, Xin-Xin Cao
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder occurring in patients of all ages from neonates to the elderly. The features of LCH are well described in children, however, they remain poorly defined in adults. There is no standard first-line treatment for adult LCH. A previous study at our institution showed that methotrexate combined with a low dose cytarabine regimen was effective but with high hematologic toxicity. Aims: This study was designed to evaluate the efficacy and safety of a low dose cytarabine regimen treatment in adults. Methods: This phase 2, prospective, single-center study enrolled 59 newly diagnosed adults multisystem (MS)-LCH or LCH with multifocal single system (SS-m) involved from October 2019 to January 2022 (NCT 04121819). The low dose cytarabine regimen was injected subcutaneously as cytarabine 0.1g/m2 (body surface) day 1-5 every 5 weeks for a cycle and 12 cycles in total. The primary endpoint was event-free survival (EFS). Events were defined as a poor response to chemotherapy, reactivation after chemotherapy or death from any cause. Results: The median age was 33 years (range 18-64 years). Thirty-nine patients were male (66.1%). Thirteen patients were SS-m LCH (22.0%), and 46 patients were MS LCH (78.0%). The most common organ involved in the total cohort was bone (74.6%), followed by lung (50.8%), pituitary (40.7%) and lymph nodes (27.1%). Thirteen patients had liver involvement (22.0%), 2 patients with spleen involvement (3.4%), no patients had hematologic involvement. All patients received at least three courses of chemotherapy, with median 12 (3-12) courses. Overall, 43 patients (72.9%) completed protocol treatment, and 16 patients (27.1%) went off protocol (9 patients’ decision, 5 poor response, 1 lost follow-up, 1 death). The overall response rate was 89.8%, including 15 patients (25.4%) achieving complete remission and 38 patients (64.4%) achieving partial remission. After a median follow-up of 25 months (range 3-41 months), 2 (3.4%) patients died of progression disease and 14 (23.7%) patients relapsed. The estimated 2-year OS and EFS were 98.3% and 73.0%, respectively. To evaluate the prognostic factors of EFS using univariate analysis, lung involvement and 3 or more organs involved at baseline had significantly shorter EFS. EFS were also evaluated using multivariate Cox regression model, lung involvement remained predictive of poorer EFS (P = 0.036; HR 0.247, 95% CI 0.066–0.915). The most common toxicity was hematological adverse events and gastrointestinal complications. 33 patients (55.9%) experienced neutropenia or thrombocytopenia. 7 patients (11.9%) had grade 4 neutropenia; 8 patients (13.6%) had grade 3 neutropenia. Only 1 patient (1.7%) had grade 4 thrombocytopenia; No patients experienced febrile neutropenia. 33 patients (55.9%) developed nausea, and 1 of them were grade 3. Vomiting occurred in 16 patients (27.1%) and constipation in 1 patient (1.7%), and none of them was grade 3-4. All gastrointestinal complications improved with supportive treatment. Alanine aminotransferase increases occurred in 6 patients (10.2%) with grade 1-2 events. and achieved a full recovery. Summary/Conclusion: Low dose cytarabine regimen is an efficient and safe regimen for newly diagnosed adult LCH. The involvement of lung at baseline indicates a worse prognosis in adult LCH.Keywords: Langerhans Cell Histiocytosis, Chemotherapy